Project Summary. More people in the United States are addicted to cannabis than to any other illicit drug, and prevalence of its use is rising, accompanied by a decline in its perceived harm among adolescents. Important maturational changes in prefrontal cortex during adolescence may make youth more vulnerable than adults to adverse effects from cannabis. Indeed, research shows impairments in memory performance and decision-making abilities of heavy cannabis users, most of whom initiate use during adolescence. However, little is known about how decision-making and memory are affected across the trajectory from initial experimentation to development of cannabis addiction. Furthermore, there is controversy in the scientific literature on whether the impairments in decision-making observed among heavy cannabis users are due to the harmful effects of cannabis on brain functioning, or whether they may be an antecedent risk factor for the development of cannabis addiction. The principal goals of this proposal are to determine whether: a) decision-making is an antecedent risk factor for cannabis addiction; and b) what changes occur in decision-making and episodic memory along different cannabis use trajectories. Participants will be 480 youth ages 14 to 15 at baseline, most of whom will have experimented with cannabis, but have yet to develop addiction. Over three years, their performance will be assessed on measures of decision-making and episodic memory every 18 months and on their substance use and symptoms of cannabis addiction every 9 months. Poorer decision-making at baseline is hypothesized to be associated with increased risk of developing cannabis addiction during follow-up. Similarly, declines in decision- making during follow-up are hypothesized to be associated with increased severity of cannabis addiction (i.e., more compulsive use and more negative consequences). Finally, those who escalate in their cannabis consumption over time will show greater deterioration in their episodic memory than observed in other (non-escalating or desisting) cannabis use trajectories. In contrast, decision-making will show little change across all trajectories, consistent with its hypothesized role as an antecedent, rather than a consequence, of cannabis addiction. Understanding more about the links between neuropsychological functions and cannabis addiction will help clarify theoretical models pertaining to their temporal association. Clinically, knowing more about neuropsychological predictors and sequelae of addiction will help us to develop more targeted and tailored interventions and prevention programs, consistent with NIDA's goals. Importantly, our findings will clarify whether decision-making is an antecedent risk factor for cannabis use and addiction, a consequence of use, or both.